Which type of mutation accounts for the sickle cell beta-globin substitution?

• A. Nonsense mutation
• B. Missense mutation
• C. Frameshift mutation
• D. Splice site mutation

Answer: (B)

A single base substitution that changes one amino acid in the protein is called a missense mutation. In sickle cell disease, the beta-globin gene changes a codon so that glutamic acid at position 6 is replaced by valine (GAG to GTG). This alters the chemical properties of the amino acid in that part of the protein, promoting polymerization of deoxygenated hemoglobin and causing red blood cells to sickle. It’s not a nonsense mutation (which would create a premature stop codon), not a frameshift (which would disrupt the reading frame with insertions/deletions), and not a splice-site mutation (which would affect RNA processing). The key point is that a single amino acid change alters protein function.